Effect of SL-573 on several functions of rat polymorphonuclear leucocytes and mast cells

Abstract

SL-573 (1-cyclopropylmethyl-4-phenyl-6-methoxy-2(1H)-quinazolinone) was tested for its effect on the chemotaxis, phagocytosis, phagocytosis-stimulated oxygen uptake and lysosomal enzyme release of rat polymorphonuclear leucocytes and the histamine release from rat mast cells. In phagocytosis, SL-573 did not show significant inhibitory activity (less than 25% even at a high concentration of 200 μM). The effects of other nonsteroidal anti-inflammatory agents on phagocytosis were also insignificant as follows: indomethacin (IM): no effect at 400 μM and 50 ?? 80% inhibition at 800 μM, mepirizole(MP) : about 25% inhibition at 1000 μM, aspirin (AS): no effect at 1000 μM, and ibuprofen (IP) : no effect at 1000 μM. SL-573, on the other hand, apparently inhibited other functions of polymorphonuclear leucocytes and mast cells at concentrations below 100 μM. Particularly, SL-573 was a potent inhibitor of phagocytosis-stimulated oxygen uptake (IC₅₀: 23 μM). The inhibitory activity of SL-573 was 17 times that of IM and more than 40 times those of IP, MP and AS. In chemotaxis, SL-573 showed 50% inhibition at 58 μM, while IC₅₀ values of IM, IP, MP and AS were 31 μM, 68 μM, 370 μM and 460 μM, respectively. The inhibitory effect of SL-573 on lysosomal enzyme release was 49.5% at 100 μM. The inhibitory activity was more potent than those of IM (100 μM: 11.8% inhibition) and IP (100 μM: 20.2%). AS and MP did not significantly affect the lysosomal enzyme release at 100 μM. In histamine release from mast cells, SL-573 showed more potent inhibitory activity (100 μM: 35-58% inhibition) than IM (300μM: 43 ?? 58%), IP (1000μM: 49 ?? 51%), AS (1000 μM: 1 ?? 5%) and MP (1000 μM: 1 ?? 41%).